The goal of this project is to develop novel therapy for prostate cancer. We propose to develop novel antibody-based therapeutics with high specificity for a target tumor cell. The tumor-selective antibody approach can be adapted for many antibodies and tumor types. Treatment of many solid tumors with antibodies is challenging due to difficulties with tumor-selective delivery. Proteins, to which monoclonal antibodies specifically bind, are usually over expressed on surface of cancer cells but also expressed, to some degree, on normal cells. Such expression pattern creates difficulties in the antibody delivery and decreases specificity of the therapy. The therapeutic efficacy of some antibodies is also limited due to toxicity. Higher amounts of antibodies are required to achieve the desired effects and result in increased side effects and higher cost of treatment. To improve the therapeutic efficacy, the local concentration of an antibody in a tumor site has to be increased without causing side effects. The proposed antibody-based product is activated in the tumor site and its concentration can reach levels that have desired therapeutic effects without systemic toxicity. There is urgent clinical need to enhance the efficacy of anticancer antibodies to achieve desirable cure rates for the disease. In Phase I, we will develop proposed reagents and test them invitro. In Phase II, we will test the reagents in preclinical studies evaluating treatment of tumors in animals.